PROJECT SUMMARY A variety of evidence suggests that sleep and circadian rhythms influence the development of alcohol use disorders (AUDs) during adolescence. However, the precise mechanisms underlying the relationships between sleep/circadian function and AU remain unknown, and thus are the focus of this application. Specifically, we hypothesize that adolescent sleep and circadian disturbances result in dysregulated reward function (i.e., diminished impulse control and increased reward sensitivity), which in turn leads to increased AU. Our proposed study will examine the short-term causal dynamics between sleep/circadian factors, reward function, and AU, thereby informing the development of novel prevention and intervention approaches for AUDs. In particular, we propose a prospective, mixed-methods approach in a sample of 150 12th grade (17-19 y/o) students reporting weekly AU. The novel design combines state-of-the-art in vivo methods (to enhance ecological validity and precision, while limiting recall bias) and laboratory methods (to enhance scientific rigor). Specifically, we will collect (1) 8 days of ecological momentary assessment (self-reported craving and AU), (2) objective measurements of sleep and endogenous circadian timing (actigraphy, salivary melatonin, clock gene expression), and (3) objective measures (behavioral and fMRI) of reward function. We will also assess self- reported sleep/circadian factors, reward function, and AU at 3- and 6-month follow-ups, allowing us to examine both proximal and longitudinal associations between our key constructs of interest. Our design capitalizes on the ?natural experiment? of weekday-weekend changes in sleep, circadian rhythms, and AU. Assessing sleep/circadian factors both pre- and post-weekend will enable us to examine whether circadian alignment and/or sleep duration prospectively predict weekend AU, and vice versa. Including pre-weekend behavioral and fMRI tasks will allow us to evaluate objective measures of reward function as intervening variables between sleep/circadian factors and AU. Specific Aim 1 is to establish the extent of proximal prospective associations between sleep/circadian factors, reward function, and AU. Specific Aim 2 is to establish the extent of distal associations between sleep/circadian factors, reward function, and AU. This innovative proposal will rigorously test our novel conceptual model proposing a circadian-reward path to adolescent AUD and examining both proximal and more distal timeframes. It will have substantial impact and public health significance, with the potential to elucidate novel mechanisms of AU problems at a key developmental stage. Demonstration of a sleep/circadian influence on AU would provide scientific justification for testing empirically-supported sleep/circadian interventions to AUD prevention.